Anti-viral cytokine

IFN-y is a potent immunostimulatory and anti-viral cytokine. The frequency of specific IFN-y-secreting cells stimulated by liposomal formulations exclusively containing the CTL epitope NS 18 51 or combinations with CpG, respectively, was evaluated by ELISPOT assay. Two weeks after three immunizations, high numbers of specific IFN-y-secreting cells in mice immunized with liposomes containing NS1851 (-0.2% of total spleen cells) were detected which further increased in mice immunized with liposomal formulations containing CpG (-0.7% of total spleen cells) (Fig. lb). 

Proteins are also used clinically to treat a variety of diseases. Erythropoietin stimulates erythrocyte production in kidney dialysis and chemotherapy patients. Granulocyte stimulating factor enhances immune systems compromised by cancer treatments. Cytokines such as interferons and interleukins are used for their anti-viral and anti-tumor activities. Other proteins are used to inhibit or stimulate blood clotting. For the most part, the pharmaceutical protein industry relies on cloning native human genes and expressing and purifying their products in recombinant form. 

Interferons, IFN s belong to a group of cytokines of Mr in the range of 15.000 to 30.000. There are three types of interferons, INF-a, INF-/3 and INF-y. They are released by cells on exposure to inducing agents, such as viruses. A special property of the INF s is their anti-viral activity. 

Another group of cytokines produced by many cell types, including macrophages, in response to viral challenge is the interferons (IFN). In mammalian cells, IFN induces the synthesis of Mx proteins that can inhibit the translation of viral mRNA. Induction of Mx proteins has been used as an indirect measure of IFN activity in fish40,68. Recently, Altmann et aV cloned, sequenced and characterized the first teleost interferon gene from the zebrafish, Danio rerio, so it should soon become feasible to quantify IFN production directly as a measure of anti-viral response. 

The in vivo anti-viral activity has partially been demonstrated (Fusco et al. 2010). The in vivo experiment of polysaccharide extract fiom Echinacea purpurea, a widely consumed botanical product, indicated that mice infected with WSN influenza A and treated with E. purpurea polysaccharide extract had less weight loss than untreated mice but similar pulmonary viral titers. Echinacea-treated mice had lower systemic and pulmonary KC and IL-10 levels and lower systemic IFN-y levels following influenza infection. These suggest that E. purpurea alters the clinical course of influenza infection in mice through modulation of cytokines and not direct antiviral activity. 

Treatment of infection antibiotic, anti-viral and anti-fungal therapy, adjuvants including cytokines, immunoglobulins and granulocyte transfusions. 

Inhibition of immunomodulatory cytokines (Fig. 1) Anti-T-cell receptor antibodies Muromonab (OKT3, Orthoclone ) binds to the CD3 complex of the T-cell receptor and induces depletion of T-lymphocytes. It is applied to prevent acute rejection of kidney, liver, and heart allografts. Rapid side effects (within 30-60 min) include a cytokine release syndrome with fever, flu-like symptoms, and shock. Late side effects include an increased risk of viral and bacterial infections and an increased incidence of lymphproliferative diseases due to immunosuppression. 

Anti-hepatitis B virus activity in vitro and in vivo was also found in wogonin and baicalein (Fig. 4), the major active constituents of the traditional Chinese medicine Scutellaria radix.More recently, Blach-Olszewska et al investigated the effect of baicalein and wogonin on two important mechanisms of innate immunity The secretion of cytokines, and the natural resistance of human leukocytes to viral infection. The results obtained indicate that these fiavonoids modulate cytokine production, that is they inhibit interferons-a and -y, and stimulate tumor necrosis factor-a and interleukin production. They also augment the resistance of peripheral blood leukocytes to the vesicular stomatitis virus. 

Tumour necrosis factor-a (TNFa) accumulates in the brain after trauma. This cytokine is known to be an important factor in delayed CNS damage. It was found that, in addition to its anti-NMDA effect, HU-211 causes up to 90% inhibition of the TNFa surge after closed head injury in rats [195], Bacterial and viral infections of the CNS are known to cause secretion of the TNFa as well as interleukin-1 and other cytokines which are involved in the inflammatory process and may cause secondary damage. Such infections may result in high mortality. It was found that rats infected with Streptococcus pneumoniae suffered less cerebral oedema on treatment with a combination of a suitable antibiotic with HU-211 than the antibiotic alone [196],... 

As previously mentioned, interferons are cytokines produced by cells to protect them from viral infection, and anti-interferon strategies are a part of the immune evasion repertoire of most viruses. These mechanisms include the production of soluble versions of interferon receptors, which act as decoys. These decoys bind and inactivate interferons before they reach their destination - normal, membrane-bound receptors.22... 

---